Brain monoamine oxidase A inhibition in cigarette smokers

Abstract

Several studies have documented a strong association between smoking and depression. Because cigarette smoke has been reported to inhibit monoamine oxidase (MAO) A in vitro and in animals and because MAO A inhibitors are effective antidepressants, we tested the hypothesis that MAO A would be reduced in the brain of cigarette smokers. We compared brain MAO A in 15 nonsmokers and 16 current smokers with [11C]clorgyline and positron emission tomography (PET). Four of the nonsmokers were also treated with the antidepressant MAO inhibitor drug, tranylcypromine (10 mg/day for 3 days) after the baseline PET scan and then rescanned to assess the sensitivity of [11C]clorgyline binding to MAO inhibition. MAO A levels were quantified by using the model term lambda k3 which is a function of brain MAO A concentration. Smokers had significantly lower brain MAO A than nonsmokers in all brain regions examined (average reduction, 28%). The mean lambda k3 values for the whole brain were 0.18 +/- 0.04 and 0.13 +/- 0.03 ccbrain (mlplasma)-1 min-1 for nonsmokers and smokers, respectively; P < 0.0003). Tranyl-cypromine treatment reduced lambda k3 by an average of 58% for the different brain regions. Our results show that tobacco smoke exposure is associated with a marked reduction in brain MAO A, and this reduction is about half of that produced by a brief treatment with tranylcypromine. This suggests that MAO A inhibition needs to be considered as a potential contributing variable in the high rate of smoking in depression and in the development of more effective strategies for smoking cessation.

Figures

Figure 1

Comparison of MAO A levels in the thalamus (as expressed by the model term λk3) for nonsmokers (n = 15), smokers (n = 16), and nonsmokers who were treated with tranylcypromine (n = 4).

Figure 2

Pixel by pixel images of the model term which is a function of MAO A activity for a nonsmoker (Top row), a smoker (Middle row), and the same nonsmoker after treatment with tranylcypromine (Bottom row). The same four planes of the brain are shown for each subject and correspond to brain sections at 5.8 cm (level of the occipital cortex and the lateral ventricles), 5.1 cm (level of the occipital cortex and the lateral ventricles), 4.5 cm (level of the thalamus), and 1 cm (level of the lower temporal poles and the cerebellum) above the canthomeatal line (proceeding from left to right). The color scale represents values of λk3 [scales from 0.4 (red) to 0 (black)]. The values of λk3 for the thalamus are 0.319, 0.212, and 0.128 ccbrain (mlplasma)−1 min−1 for the nonsmoker, the smoker and the nonsmoker treated with tranylcypromine, respectively. The corresponding K1 values are 0.434, 0.421, 0.404 ml/cc/min.